Blood vessel formation processes are largely classified into two types, namely vasculogenesis, in which angioblasts or vascular progenitor cells differentiate to form a primitive vascular network, and angiogenesis, in which new blood vessels are formed from existing vessels. During vasculogenesis, vascular progenitor cells differentiate into vascular endothelial cells and the like, yielding principal blood vessels. Vasculogenesis may include, depending on the pattern of differentiation of vascular progenitor cells, Type 1 vasculogenesis, in which vascular endothelial cells differentiate in situ, as in the production of blood vessels in the body, and Type 2 vasculogenesis, which occurs when vascular progenitor cells migrate over some significant distance and then differentiate, as in the formation of blood vessels in the endocardium or the cranial region. This acts as an important mechanism in various pathological states of inflammation, tumors and the like, as well as physiological states such as wound healing, ovulation, and pregnancy, including the fetal development process, and is thus under study.
Vascular injury causes a variety of ischemic diseases, and may be fundamentally treated through restoration of endogenous cells or transplantation of functional vascular cells for forming blood vessels. In this regard, treatment through the transplantation of functional vascular cells is problematic because effective methods of differentiating vascular cells are not readily available and because it is difficult to obtain large amounts of cells.
Also, methods of inducing the differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells into vascular cells have been proposed, but are disadvantageous because the efficiency of induction into cells of interest is low and there is the risk of activating tumor genes from the embryonic stem cells or pluripotent stem cells upon differentiation into specific cells. Furthermore, although induced pluripotent stem cells are able to avoid ethical issues associated with embryonic destruction and are resistant to immune system rejection when transplanted, they are undesirably liable to form teratoma, as in the embryonic stem cells.
Also, methods of preparing vascular progenitor cells from somatic cells through direct transdifferentiation have not yet been reported. In particular, the establishment of multipotency of vascular cells by direct transdifferentiation of somatic cells through transduction of ETV2 (ETS variant gene 2) or FLI1 (Friend leukemia virus integration 1) is not known.